Causes and Risk Factors
Diabetic neuropathy is caused by a combination of the direct effects of high blood sugar on nerve cells as well as damage to the small blood vessels that provide blood to the nerves (Feldman 2012b; Edwards 2008). Not surprisingly, the main risk factor for diabetic neuropathy is poor control of blood glucose levels (Feldman 2012b; Edwards 2008; Booya 2005; Forrest 1997). Poor blood glucose control allows blood glucose levels to stay high, damaging both nerves and blood vessels. Consequently, many markers of poor blood glucose control, such as fasting blood glucose and hemoglobin A1C (HbA1C; a marker of long term blood glucose levels) are elevated (Fiçicioğlu 1994; Dyck 1999). Supporting this concept are data from two different studies, the Diabetes Control and Complications Trial (DCCT) and the Epidemiology of Diabetes Interventions and Complications (EDIC). The DCCT found that modifying treatment regimens to achieve tighter glycemic control led to a dramatic 60% reduction in diabetic neuropathy after five years (Genuth 2006).
Even in people who are not diabetic, high blood glucose levels caused by prediabetes may contribute to nerve damage. Prediabetes is a precursor to type 2 diabetes and is sometimes called impaired glucose tolerance or insulin resistance. People with prediabetes have blood sugar levels that are elevated, but not high enough to qualify as diabetes. People who have otherwise unexplained neuropathy are more likely to have prediabetes. In addition, people with prediabetes and neuropathy who lower their blood glucose with diet and lifestyle changes can experience improvement in their neuropathy symptoms (Callaghan 2012a). Life Extension recommends an optimal fasting blood glucose range of 70-85 mg/dL.
Other risk factors for diabetic neuropathy have been identified, though not all of them are modifiable. Height is a risk factor for diabetic neuropathy (Edwards 2008; Forrest 1997), suggesting that longer peripheral nerves are more vulnerable to damage from diabetes. Another risk factor is age, as the incidence of diabetic neuropathy increases with age. Similarly, the longer someone has had diabetes, the more likely he or she is to develop diabetic neuropathy. Male gender is also a risk factor for diabetic neuropathy (Edwards 2008; Booya 2005). In addition, males develop diabetic neuropathy earlier than females during the course of the disease (Aaberg 2008).
Many of the other risk factors for diabetic neuropathy are preventable, especially because they pertain to overall cardiovascular health. Due to the role that vascular problems play in diabetic neuropathy, it is not surprising that many of the other risk factors for this complication of diabetes are risk factors for cardiovascular disease. High plasma levels of triglycerides, high body mass index (BMI; a measure of weight relative to height), high blood pressure, diabetic retinopathy, smoking, and excessive alcohol use are all associated with an increased risk of diabetic neuropathy (Booya 2005; Edwards 2008; Feldman 2012b; Forrest 1997; Dyck 1999; Wiggin 2009; Nie 2012). Having clinically diagnosed cardiovascular disease doubles the risk of diabetic neuropathy, regardless of the other risk factors. In addition to the content reviewed here, individuals with diabetic neuropathy are encouraged to read the Life Extension protocol on Atherosclerosis and Cardiovascular Disease, as it contains numerous evidence-based strategies to help promote optimal cardiovascular health.